title: 1α,25-Dihydroxycholecalciferol (Vitamin D3) induces NO-dependent endothelial cell proliferation and migration in a three-dimensional matrix.
abstract: OBJECTIVE
  The 1α,25-dihydroxycholecalciferol (Vit. D) induces eNOS dependent nitric oxide (NO) production in human umbilical vein endothelial cells (HUVEC). To our knowledge, there are no reports directly relating Vit. D induced NO production to proliferation and/or migration in endothelial cells (EC). The aim of this study was to evaluate whether Vit. D addition to porcine EC could affect their proliferation and/or migration in a three-dimensional matrix via NO production.
  
  
  METHODS
  Porcine aortic endothelial cells (PAE) were used to evaluate Vit. D effects on cell proliferation and migration in a three-dimensional matrix.
  
  
  RESULTS
  Vit. D induced NO production in PAE cells. Moreover, it induced a significant increase in cellular proliferation and migration in a three-dimensional matrix. These effects were NO dependent, as inhibiting eNOS activity by L-NAME PAE migration was abrogated. This effect was strictly related to MMP-2 expression and apparently dependent on Vit. D and NO production.
  
  
  CONCLUSIONS
  Vit. D can promote both endothelial cells proliferation and migration in a three-dimensional matrix via NO-dependent mechanisms. These findings cast new light on the role of Vit. D in the angiogenic process, suggesting new applications for Vit. D in such fields as tissue repair and wound healing.
authors.affiliation: Translational Medicine Department, University of Eastern Piedmont A. Avogadro, Via Solaroli 17, Novara, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Molinari
authors.forename: Manuela
authors.initials: M
authors.lastname: Rizzi
authors.forename: Diletta F
authors.initials: DF
authors.lastname: Squarzanti
authors.forename: Pamela
authors.initials: P
authors.lastname: Pittarella
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vacca
authors.forename: Filippo
authors.initials: F
authors.lastname: Renò
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D013552:Swine
chemical_list: D002762:Cholecalciferol; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D020778:Matrix Metalloproteinase 2; D019331:NG-Nitroarginine Methyl Ester